Sección de Estudios de Posgrado e Investigación y Departamento de Bioquímica, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, Miguel Hidalgo, Distrito Federal, México.
Curr Drug Metab. 2011 Jul;12(6):533-48. doi: 10.2174/138920011795713670.
Cytochrome P450 (CYP) 2C9 is the principal isoform of the CYP2C subfamily in the human liver and is involved in the oxidation of several endogenous and xenobiotic compounds, including many therapeutic drugs. The metabolism of drugs by CYP2C9 can yield either safe or toxic products, which may be related to the recognition and binding modes of the substrates to this isoform. These interactions can be studied using in silico methods such as quantum chemistry, molecular dynamics and docking simulations, which can also be useful for predicting the structure of metabolites. In these types of studies, the ligand and the protein must be tridimensional models; thus, the protein can be built by homology modeling or retrieved from the Protein Data Bank. Therefore, the current review emphasizes the importance of using in silico methods to predict the metabolism of CYP2C9 because these computational tools have allowed the description of the principal characteristics of the active site of this isoform at the molecular level and the chemical properties of its ligands.
细胞色素 P450（CYP）2C9 是人类肝脏中 CYP2C 亚家族的主要同工酶，参与多种内源性和外源性化合物的氧化，包括许多治疗药物。CYP2C9 对药物的代谢可以产生安全或有毒的产物，这可能与底物与该同工酶的识别和结合模式有关。这些相互作用可以使用量子化学、分子动力学和对接模拟等计算方法进行研究，这些方法也可用于预测代谢产物的结构。在这些类型的研究中，配体和蛋白质必须是三维模型；因此，蛋白质可以通过同源建模构建，也可以从蛋白质数据库中检索。因此，本综述强调了使用计算方法预测 CYP2C9 代谢的重要性，因为这些计算工具允许在分子水平上描述该同工酶活性部位的主要特征及其配体的化学性质。
